Transmission of Helicobacter pylori between a human and two dogs: A case report.

BACKGROUND: Whereas non-Helicobacter pylori helicobacters, which are frequently detected in the stomachs of dogs and cats as a source of zoonoses, have attracted considerable attention, the role of pets in H. pylori epidemiology is unclear. In our previous study, an H. pylori infection was detected in the stomach of a dog (Dog 1). Here, we investigated the H. pylori infection status in the female offspring of Dog 1 (Dog 2) and its owner within the same household. MATERIALS AND METHODS: Biopsy specimens were obtained from the dog's owner and tested for H. pylori. DNA from gastric biopsy samples of Dog 1, gastric fluid sediment of Dog 2, and bacteria from the stomach of the owner was obtained, and Helicobacter genus- and species-specific PCRs were performed. Then, sequence analyses of the partial region of the ureAB gene were conducted. RESULTS: Samples from both dogs and the owner reacted positively in the genus-specific PCR and negative in the Helicobacter felis-, Helicobacter bizzozeronii-, and Helicobacter heilmannii sensu stricto-specific PCRs. All three samples also reacted positively in the H. pylori-specific PCR. Sequences of the partial ureAB gene from all subjects were identical. CONCLUSIONS: The results suggested that the two dogs and their owner were infected with an identical H. pylori strain. This report is the first to demonstrate that H. pylori can be transmitted between humans and dogs. Further studies are required to investigate the risk factors for the transmission of H. pylori between humans and dogs from the perspective of preventive epidemiology.

Assessment of HER2 Expression in Canine Urothelial Carcinoma of the Urinary Bladder.

Canine urothelial carcinoma (UC) has a poor prognosis and high metastatic rate. Human epidermal growth factor receptor 2 (HER2), a receptor tyrosine kinase involved in cell proliferation and differentiation regulation, has been attracting interest as a therapeutic target molecule for human breast cancer. This study investigated expression of the canine homolog of HER2 (ERBB2) in canine UC, and its association with clinical factors. Since it has been controversial whether commercial anti-human HER2 antibody (Dako A0485) correctly recognizes the canine homolog of HER2, an application of the antibody using a canine UC cell line was validated first. By Western blot, a single band at the appropriate size for canine HER2 (185 kDa) was recognized. Immunohistochemistry for HER2 was performed on 23 samples of UC, 8 samples of polypoid cystitis, and 8 samples of normal urinary bladder, and the results were scored as either 0, 1+, 2+, or 3+ with reference to the evaluation method for human UC. Intense membranous HER2 immunoreactivity was frequently observed in neoplastic cells, especially in grade 2 UC. Minor HER2 expression was found in the epithelial cells of polypoid cystitis and normal bladder. The incidence of HER2 positivity (scores of 2+ or 3+) was 14 of 23 (60.9%) in UC, 3 of 8 (37.5%) in polypoid cystitis, and 0 of 8 (0%) in normal bladder. There was no significant correlation between HER2 positivity and clinical factors. While increased HER2 expression was observed in a subset of urothelial carcinomas, further mechanistic studies are needed to determine its role in the pathogenesis and targeted therapy of this cancer.

Comprehensive gene expression analysis of canine invasive urothelial bladder carcinoma by RNA-Seq.

BACKGROUND: Invasive urothelial carcinoma (iUC) is a major cause of death in humans, and approximately 165,000 individuals succumb to this cancer annually worldwide. Comparative oncology using relevant animal models is necessary to improve our understanding of progression, diagnosis, and treatment of iUC. Companion canines are a preferred animal model of iUC due to spontaneous tumor development and similarity to human disease in terms of histopathology, metastatic behavior, and treatment response. However, the comprehensive molecular characterization of canine iUC is not well documented. In this study, we performed transcriptome analysis of tissue samples from canine iUC and normal bladders using an RNA sequencing (RNA-Seq) approach to identify key molecular pathways in canine iUC. METHODS: Total RNA was extracted from bladder tissues of 11 dogs with iUC and five healthy dogs, and RNA-Seq was conducted. Ingenuity Pathway Analysis (IPA) was used to assign differentially expressed genes to known upstream regulators and functional networks. RESULTS: Differential gene expression analysis of the RNA-Seq data revealed 2531 differentially expressed genes, comprising 1007 upregulated and 1524 downregulated genes, in canine iUC. IPA revealed that the most activated upstream regulator was PTGER2 (encoding the prostaglandin E2 receptor EP2), which is consistent with the therapeutic efficiency of cyclooxygenase inhibitors in canine iUC. Similar to human iUC, canine iUC exhibited upregulated ERBB2 and downregulated TP53 pathways. Biological functions associated with cancer, cell proliferation, and leukocyte migration were predicted to be activated, while muscle functions were predicted to be inhibited, indicating muscle-invasive tumor property. CONCLUSIONS: Our data confirmed similarities in gene expression patterns between canine and human iUC and identified potential therapeutic targets (PTGER2, ERBB2, CCND1, Vegf, and EGFR), suggesting the value of naturally occurring canine iUC as a relevant animal model for human iUC.

In situ detection of GM1 and GM2 gangliosides using immunohistochemical and immunofluorescent techniques for auxiliary diagnosis of canine and feline gangliosidoses.

BACKGROUND: GM1 and GM2 gangliosidoses are progressive neurodegenerative lysosomal storage diseases resulting from the excessive accumulation of GM1 and GM2 gangliosides in the lysosomes, respectively. The diagnosis of gangliosidosis is carried out based on comprehensive findings using various types of specimens for histological, ultrastructural, biochemical and genetic analyses. Therefore, the partial absence or lack of specimens might have resulted in many undiagnosed cases. The aim of the present study was to establish immunohistochemical and immunofluorescent techniques for the auxiliary diagnosis of canine and feline gangliosidoses, using paraffin-embedded brain specimens stored for a long period. RESULTS: Using hematoxylin and eosin staining, cytoplasmic accumulation of pale to eosinophilic granular materials in swollen neurons was observed in animals previously diagnosed with GM1 or GM2 gangliosidosis. The immunohistochemical and immunofluorescent techniques developed in this study clearly demonstrated the accumulated material to be either GM1 or GM2 ganglioside. CONCLUSIONS: Immunohistochemical and immunofluorescent techniques using stored paraffin-embedded brain specimens are useful for the retrospective diagnosis of GM1 and GM2 gangliosidoses in dogs and cats.

Complex malformations of the urogenital tract in a female dog: Gartner duct cyst, ipsilateral renal agenesis, and ipsilateral hydrometra.

A 10-month-old female toy poodle was referred to the University of Tokyo Veterinary Medical Center with a urogenital anomaly found during sterilization. An exploratory laparotomy revealed a cyst adhering to the cervix and a unilateral renal agenesis. Histopathology and immunohistochemical analysis of the cyst was consistent with remnants of the Wolffian duct or a Gartner duct cyst. This is a rare case of a canine Gartner duct cyst with renal agenesis and uterine anomaly. We discuss the similarity of this case to that of humans and introduce a classification in the literature for these complex urogenital malformations for further clinical research into the precise diagnosis and appropriate surgical planning.

Bladder Reconstruction in Cats Using In-Body Tissue Architecture (iBTA)-Induced Biosheet.

Urinary tract diseases are common in cats, and often require surgical reconstruction. Here, to explore the possibility of urinary tract reconstruction in cats using in-body tissue architecture (iBTA), biosheets fabricated using iBTA technology were implanted into the feline bladder and the regeneration process was histologically evaluated. The biosheets were prepared by embedding molds into the dorsal subcutaneous pouches of six cats for 2 months. A section of the bladder wall was removed, and the biosheets were sutured to the excision site. After 1 and 3 months of implantation, the biosheets were harvested and evaluated histologically. Implantable biosheets were formed with a success rate of 67%. There were no major complications following implantation, including tissue rejection, severe inflammation, or infection. Urinary incontinence was also not observed. Histological evaluation revealed the bladder lumen was almost entirely covered by urothelium after 1 month, with myofibroblast infiltration into the biosheets. After 3 months, the urothelium became multilayered, and mature myocytes and nerve fibers were observed at the implantation site. In conclusion, this study showed that tissue reconstruction using iBTA can be applied to cats, and that biosheets have the potential to be useful in both the structural and functional regeneration of the feline urinary tract.

Pan-tumour analysis of COX-2 expression in dogs.

Cyclooxgenase-2 (COX-2) is associated with inflammatory microenvironment and tumour progression. COX-2 expression was reported in canine tumours, and anti-COX treatment showed therapeutic effects in selected tumour types. Currently, direct comparisons between different tumour types or reports were impossible due to varying evaluation protocols. Additionally, COX-2 expression in relatively uncommon tumours were yet to be evaluated. Here, we analysed COX-2 expression across various tumour types in dogs in a consistent protocol, aiming to revisit accumulated evidence in the field and report novel candidate tumours for anti-COX therapy. COX-2 expression in 32 histological types of tumours, which consisted of 347 samples in total, was investigated using immunohistochemistry followed by the Belshaw's method scoring (range: 0-12). More than the half of the samples expressed COX-2 in mast cell tumours, transitional cell carcinoma in the urinary tract, squamous cell carcinoma, liposarcoma, and melanoma, with COX-2 median scores ranging from 1-8. On the other hand, <20% tissues expressed COX-2 in the half of tumour types investigated. Overall COX-2 positive rate was 27%. In conclusion, the results confirmed COX-2 expression in the well-known COX-2-expresing tumour types and suggested novel candidate tumours for anti-COX-2 therapy. At the same time, overall COX-2 expression was low, and inter- and intra-histology heterogeneity was apparent. This study will provide a foundation reference for future research in canine tumours.

Clinical characteristics and outcomes of Mott cell lymphoma in nine miniature dachshunds.

BACKGROUND: Lymphoma with Mott cell change, or Mott cell lymphoma (MCL), is an uncommon variant of canine lymphoma. Because of its rare occurrence, there has been no comprehensive study describing the disease so far. Miniature dachshunds, a popular breed in Japan, sometimes experience MCL. OBJECTIVES: To investigate the clinical characteristics and outcomes of MCL in miniature dachshunds. METHODS: Medical records were retrospectively reviewed to identify miniature dachshunds diagnosed with MCL and other types of lymphoma. Data on clinical and laboratory findings, treatments and outcomes were collected. Survival times were compared between miniature dachshunds with MCL and other types of lymphoma. RESULTS: Of the 87 miniature dachshunds diagnosed with lymphoma, 9 (10%) had cytological characteristics of MCL. All 9 miniature dachshunds with MCL were categorised as having alimentary lymphoma (small and/or large intestine, 6 dogs; mesenteric lymph node, 3 dogs). The median age was 3.1 years (range, 2.0-9.4 years). All nine dogs were treated with chemotherapeutic protocols used for large cell lymphoma or alkylating agents such as melphalan or chlorambucil. The overall response rate to initial chemotherapy was 78%, and the median progression-free survival was 105 days. Overall survival in these nine dogs ranged from 6 to >1513 days (median, 240 days), which was significantly longer than in 29 miniature dachshunds with alimentary large cell lymphoma other than MCL (median, 57 days; p = 0.0491). CONCLUSIONS: MCL in miniature dachshunds can be recognised as a peculiar type of B-cell lymphoma occurring in relatively young dogs as an alimentary form and has a longer survival compared with typical alimentary large cell lymphoma.

MUC5AC and MUC5B expression in canine gallbladder mucocele epithelial cells.

Gallbladder mucocele (GBM) is one of the most common gallbladder diseases in dogs. Its pathogenesis has not yet been clarified, but excessive accumulation of a secretory gel-forming mucin, MUC5AC in the gallbladder has been reported. This study aimed to ascertain if MUC5AC overproduction resulted in mucus accumulation in the gallbladder during GBM development. Eleven dogs undergoing cholecystectomy who were pathologically diagnosed with GBM were included, and the expression level of mucins, particularly MUC5AC and MUC5B, in their gallbladder epithelial cells was compared with those in normal gallbladder epithelial cells. On reverse transcription-quantitative polymerase chain reaction screening, there was a significant difference (P<0.05) in the mRNA expression level of MUC1, but not of other mucins including MUC5AC and MUC5B, between mucocele and normal gallbladder epithelial cells. Protein expression levels were also evaluated for MUC5AC and MUC5B using immunohistochemistry. There was little immunoreactivity for MUC5AC, whereas MUC5B showed definitive staining in gallbladder epithelial cells. There was no difference in MUC5AC and MUC5B protein expression levels between mucocele and normal gallbladder epithelial cells. These data suggest that excessive production of mucin, especially MUC5AC and MUC5B, does not occur in canine GBM, and that abnormal mucus excretion, rather than excessive mucus production, may be the cause of GBM development.

Serum level of apoptosis inhibitor of macrophage in dogs with histiocytic sarcoma and its association with the disease.

Histiocytic sarcoma (HS) is a rare neoplasm of macrophages or dendritic cells with a poor prognosis in dogs. As the apoptosis inhibitor of macrophage (AIM) is characteristically expressed in canine macrophages, we hypothesised that AIM is involved in the development or progression of HS in dogs. In this study, AIM expression in the tumour region and serum AIM levels in dogs with HS was assessed. Additionally, the effects of AIM overexpression on HS cell viability were investigated using a HS cell line that was selected from five validated HS cell lines. Immunohistochemistry showed that AIM expression was observed in the cytoplasm of the HS cells. CD36, a candidate AIM receptor, was also observed on the cell membrane of HS cells. When the serum AIM level was detected in 36 dogs with HS and 10 healthy dogs via western blot analysis, the AIM levels in the HS dogs were significantly higher than those in the controls. AIM mRNA expression in the 5 HS cell lines varied but was higher than that in the other tumour-derived lines. Among the five HS cell lines, DH82 originally had lower AIM and the highest CD36 expression. When AIM was overexpressed in DH82, therein cell growth speed and invasion, apoptosis inhibition and phagocytic activity were strongly upregulated. These data suggest that elevated intra-tumour expression of AIM could induce the progression of HS cells in dogs. Moreover, elevated serum AIM levels in dogs with HS could serve as a biomarker of HS.

Podoplanin Drives Amoeboid Invasion in Canine and Human Mucosal Melanoma.

Mucosal melanoma metastasizes at an early stage of the disease in human and dog. We revealed that overexpression of podoplanin in tumor invasion fronts (IF) was related to poor prognosis of dogs with mucosal melanoma. Moreover, podoplanin expressed in canine mucosal melanoma cells promotes proliferation and aggressive amoeboid invasion by activating Rho-associated kinase (ROCK)-myosin light chain 2 (MLC2) signaling. PDPN-ROCK-MLC2 signaling plays a role in cell-cycle arrest and cellular senescence escape as a mechanism for regulating proliferation. Podoplanin induces amoeboid invasion in the IFs of mouse xenografted tumor tissues, similar to canine mucosal melanoma clinical samples. We further identified that podoplanin expression was related to poor prognosis of human patients with mucosal melanoma, and human mucosal melanoma with podoplanin-high expression enriched gene signatures related to amoeboid invasion, similar to canine mucosal melanoma. Overall, we propose that podoplanin promotes canine and human mucosal melanoma metastasis by inducing aggressive amoeboid invasion and naturally occurring canine mucosal melanoma can be a novel research model for podoplanin expressing human mucosal melanoma. IMPLICATIONS: Podoplanin could be a new therapeutic target to restrict the metastatic dissemination of canine and human mucosal melanoma.

Podoplanin promotes cell proliferation, survival, and migration of canine non-tonsillar squamous cell carcinoma.

Podoplanin (PDPN) is a prognostic factor and is involved in several mechanisms of tumor progression in human squamous cell carcinoma (SCC). Canine non-tonsillar SCC (NTSCC) is a common oral tumor in dogs and has a highly invasive characteristic. In this study, we investigated the function of PDPN in canine NTSCC. In canine NTSCC clinical samples, PDPN overexpression was observed in 80% of dogs with NTSCC, and PDPN expression was related to ki67 expression. In PDPN knocked-out canine NTSCC cells, cell proliferation, cancer stemness, and migration were suppressed. As the mechanism of PDPN-mediated cell proliferation, PDPN knocked-out induced apoptosis and G2/M cell cycle arrest in canine NTSCC cells. These findings suggest that PDPN promotes tumor malignancies and may be a novel biomarker and therapeutic target for canine NTSCC.

Whole exome and transcriptome analysis revealed the activation of ERK and Akt signaling pathway in canine histiocytic sarcoma.

Histiocytic sarcoma (HS) is an incurable aggressive tumor, and no consensus has been made on the treatment due to its rare occurrence. Since dogs spontaneously develop the disease and several cell lines are available, they have been advocated as translational animal models. In the present study, therefore, we explored gene mutations and aberrant molecular pathways in canine HS by next generation sequencing to identify molecular targets for treatment. Whole exome sequencing and RNA-sequencing revealed gene mutations related to receptor tyrosine kinase pathways and activation of ERK1/2, PI3K-AKT, and STAT3 pathways. Analysis by quantitative PCR and immunohistochemistry revealed that fibroblast growth factor receptor 1 (FGFR1) is over-expressed. Moreover, activation of ERK and Akt signaling were confirmed in all HS cell lines, and FGFR1 inhibitors showed dose-dependent growth inhibitory effects in two of the twelve canine HS cell lines. The findings obtained in the present study indicated that ERK and Akt signaling were activated in canine HS and drugs targeting FGFR1 might be effective in part of the cases. The present study provides translational evidence that leads to establishment of novel therapeutic strategies targeting ERK and Akt signaling in HS patients.

Retrobulbar primitive neuroectodermal tumor in a squirrel monkey (Saimiri sciureus).

BACKGROUND: A 2.8-year-old female captive-bred common squirrel monkey (Saimiri sciureus) showed exophthalmos of the right eye, and the eye was surgically enucleated. A tumor mass was found in the eye. METHODS: Formalin-fixed tumor samples were examined histopathologically and immunohistochemically for diagnosis. RESULTS: The retrobulbar tumor mass adhered to the sclera and infiltrated the choroid. Histopathologically, tumor cells were pleomorphic, arranged in a sheet pattern, and mimicked primitive neuroectodermal cells. The tumor cells were strongly positive for precursor neuronal cell markers (beta III tubulin, neuron-specific enolase, vimentin, nestin, doublecortin, oligo2, and S-100), but negative for mature cell markers (cytokeratin, neurofilament, and glial fibrillary acidic protein) and a retinoblastoma marker (rhodopsin). CONCLUSIONS: This is the first reported case for the retrobulbar location of primitive neuroectodermal tumor in non-human primates.

Successful treatment of a lung abscess without surgical intervention in a cat.

Case summary: An 8-year-old neutered female domestic shorthair cat was referred with complaints of lethargy, anorexia, fever, tachypnoea and a pulmonary mass on thoracic radiography. Whole-body CT revealed the presence of a nodular lesion in the right caudal lobe of the lung. Fine-needle aspiration of the lung mass yielded purulent fluid and cytology showed a large number of mildly to moderately degenerated neutrophils with numerous cocci and bacilli, leading to the diagnosis of a lung abscess. Empirical administration of doxycycline and orbifloxacin was initiated on the day of referral. Bacterial culture and antibiotic susceptibility tests using the collected fluid sample detected two types of bacteria, which were susceptible to both antibiotics. The clinical signs of the cat improved after the initiation of treatment, and the antibiotics were discontinued 28 days later, after the lung lesions disappeared. No recurrence of lung abscess was observed until 588 days after the discontinuation of treatment. Relevance and novel information: Only one case of a lung abscess has been previously reported in cats. Furthermore, while surgical resection is the most common treatment for lung abscesses in the field of veterinary medicine, this is the first report of successful treatment with antibiotic administration alone.

Rapid visualization of mammary gland tumor lesions of dogs using the enzyme-activated fluorogenic probe; γ-glutamyl hydroxymethyl rhodamine green.

Since gamma-glutamyl transpeptidase (GGT) is highly and locally expressed in human breast cancer, a GGT-enzymatically activatable fluorescent probe, gamma-glutamyl hydroxymethyl rhodamine green (gGlu-HMRG), has been developed to detect the human breast cancer area with high performance. In this study, GGT expression and the efficacy of gGlu-HMRG on visualization were investigated in canine mammary gland tumors (MGT). Seventeen non-fixed fresh-frozen MGT specimens and each peritumoral control tissue were utilized. The GGT mRNA levels were highly observed in the tumor specimens compared with the control. GGT immunostaining was mostly observed on the cell membrane and cytosol of the alveolar and duct mammary epithelium of MGT tissues. These signals were strongly positive in several cases while they were mild to not observed in other cases. When gGlu-HMRG solution was dropped to the non-fixed tissue pieces of MGT or control tissues, the fluorescence intensities (FIs) were measured using Maestro in-vivo imaging device. FIs in MGT tissues were significantly higher than each control tissue 20 min after treatment. Based on Youden index method, the maximum sensitivity and specificity of FI was 82.4% and 82.4%. These findings suggest that GGT is highly expressed in several MGTs in dogs and gGlu-HMRG could visualize at least a part of MGT tissues in dogs. Nevertheless, it should be needed to assess the false-negative areas more carefully in canine than human cases.

Evaluation of the degree and distribution of lymphangiectasia in full-thickness canine small intestinal specimens diagnosed with lymphoplasmacytic enteritis and granulomatous lymphangitis.

Intestinal lymphangiectasia (IL) is often observed in dogs with chronic small intestinal diseases. Hypoplasia of the lymphatic vessel due to decreased lymphangiogenesis, which has been suggested in human idiopathic IL, may contribute to the pathogenesis of canine IL. This study aimed to evaluate the diameter and number of lymphatic vessels in full-thickness small intestinal specimens of dogs with IL. Immunohistochemical labeling of lymphatic endothelial cell markers was performed on retrospectively retrieved full-thickness small intestinal specimens. Sixteen dogs with histologically confirmed IL were included, of which 10 had lymphoplasmacytic enteritis (LPE), and six had granulomatous lymphangitis (GL). Nine dogs that died from non-gastrointestinal disorders and with little or no abnormalities in the small intestine were used as controls. Lymphatic vessel diameters in dogs with IL were significantly increased in all layers of the small intestine, including the villus lacteal, lamina propria, submucosa, muscularis, and mesentery, compared with controls (all P<0.01). There was no significant difference in the lymphatic vessel diameters between dogs with LPE and GL (all P>0.05). There was no significant difference in the number of lymphatic vessels between dogs with IL and the controls in all layers of the small intestine (all P>0.05). This study demonstrated that IL was observed in all layers of the small intestine, including the submucosa, muscularis, and mesentery, independent of the underlying disease. Factors other than reduced lymphatic vessels would contribute to the pathogenesis of IL in dogs.

Association between intestinal lymphangiectasia and expression of inducible nitric oxide synthase in dogs with lymphoplasmacytic enteritis.

Intestinal lymphangiectasia (IL) is a common complication in dogs. Since nitric oxide (NO) is known to relax the lymphatic vessel, we evaluated inducible NO synthase (iNOS) expression using immunohistochemistry in 13 dogs with lymphoplasmacytic enteritis (LPE) with or without IL. The duodenal iNOS expressing cells were significantly increased in dogs with IL-negative or IL-positive LPE dogs (P=0.025, P=0.007) compared with control dogs. However, there was no significant difference in iNOS expression between IL-positive and IL-negative tissues. Based on these results, there is no clear evidence for the NO overproduction in the pathogenesis of IL in dogs with LPE. Factors other than NO could, thus, contribute to IL in dogs with LPE.

Adult-Onset Neuronal Ceroid Lipofuscinosis in a Shikoku Inu.

A two-year-and-eleven-month-old male Shikoku Inu was referred for evaluation of progressive gait abnormality that had begun three months prior. Neurological examination revealed ventral flexion of the neck, a wide-based stance in the hindlimb, wide excursions of the head from side to side, tremor in all four limbs, hypermetria in all four limbs, proprioceptive deficits in all four limbs, reduced patellar reflex in both hindlimbs, and postural vertical nystagmus. Later, behavioral and cognitive dysfunction, ataxia, and visual deficits slowly progressed. Magnetic resonance imaging revealed symmetrical progressive atrophy of the whole brain and cervical spinal cord. Bilateral retinal degeneration was observed, and both flush and flicker electroretinograms were bilaterally non-recordable at the age of five years and eight months, and the dog was euthanized. Histopathologically, faint-to-moderate deposition of light-brown pigments was frequently observed in the cytoplasm of neurons throughout the cerebrum, cerebellum, and nuclei of the brainstem. The pigments were positive for Luxol fast blue, periodic acid-Schiff, and Sudan black B, and exhibited autofluorescence. Electron microscopic examination revealed the accumulation of membranous material deposition in the neuronal cytoplasm. Small foci of pigment-containing macrophages were frequently observed around the capillary vessels. Based on these clinical and pathological findings, the animal was diagnosed with adult-onset neuronal ceroid lipofuscinosis.

Positioning Head Tilt in Canine Lysosomal Storage Disease: A Retrospective Observational Descriptive Study.

Positioning head tilt is a neurological sign that has recently been described in dogs with congenital cerebellar malformations. This head tilt is triggered in response to head movement and is believed to be caused by a lack of inhibition of the vestibular nuclei by the cerebellar nodulus and ventral uvula (NU), as originally reported cases were dogs with NU hypoplasia. We hypothesized that other diseases, such as lysosomal storage diseases that cause degeneration in the whole brain, including NU, may cause NU dysfunction and positioning head tilt. Videos of the clinical signs of canine lysosomal storage disease were retrospectively evaluated. In addition, post-mortem NU specimens from each dog were histopathologically evaluated. Nine dogs were included, five with lysosomal storage disease, two Chihuahuas with neuronal ceroid lipofuscinosis (NCL), two Border Collies with NCL, one Shikoku Inu with NCL, two Toy Poodles with GM2 gangliosidosis, and two Shiba Inus with GM1 gangliosidosis. Twenty-eight videos recorded the clinical signs of the dogs. In these videos, positioning head tilt was observed in seven of nine dogs, two Chihuahuas with NCL, one Border Collie with NCL, one Shikoku Inu with NCL, one Toy Poodle with GM2 gangliosidosis, and two Shiba Inus with GM1 gangliosidosis. Neuronal degeneration and loss of NU were histopathologically confirmed in all diseases. As positioning head tilt had not been described until 2016, it may have been overlooked and may be a common clinical sign and pathophysiology in dogs with NU dysfunction.